Intensified Rituimab Prephase Before FCR in Untreated B-CLL

March 15, 2016 updated by: French Innovative Leukemia Organisation

Phase II Multicentric, Randomized Trial, Exploring Intensified Rituximab Prephase Monotherapy Before Standard Fludarabine-Cyclophosphamide-Rituximab Regimen in Previously Untreated Symptomatic B-cell Chronic Lymphocytic Leukemia

Phase II, multicenter, randomized trial, exploring intensified Rituximab prephase monotherapy before standard Fludarabine-Cyclophosphamide-Rituximab FC-R regimen in previously untreated symptomatic B-cell chronic lymphocytic leukemia CLL.

A Study from the Goelams GCFLLCMW intergroup

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Young fit medically B Cell untreated patients Comparison between FCR treatment = 6 FCR cycles and a the addition of a prephase with R Dense treatment before the 6 FCR cycles.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
140

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
    • CLCC Henri Becquerel
      • Rouen, CLCC Henri Becquerel, France, 76038
        • Stephane LEPRETRE
    • Regional university Hospital
      • Montpellier, Regional university Hospital, France, 34295
        • Guillaume CARTRON

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria:

  • Patient information and written informed consent
  • 18 years < Age < 66 ans
  • confirmed B-CLL Matutes score 4 or 5
  • Binet stage C or Binet stage A and B with active disease could be considered for inclusion. For stage A with active disease an agreement of investigator coordinator is required.
  • no prior treatment except steroids for less than 1 month (detail corticoid)
  • No 17p deletion as assessed by FISH < 10 % positive nuclei
  • Performance status ECOG < 2
  • CIRS Cumulative Illness Rating Scale < 6

Exclusion criteria:

  • Binet stage A without active disease according to IWCLL 2008 criteria
  • Know HIV seropositivity
  • Hepatitis B or C seropositivity unless clearly due to vaccination
  • Life expectancy < 6 months
  • Clinically significant auto-immune anemia
  • Active second malignancy currently requiring treatment (except basal cell carcinoma in situ endometrial carcinoma and incidental prostate carcinoma) and/or less than 5 years CR after breast cancer
  • Any severe co-morbid conditions such as Class III or IV heart failure, myocardial infarction within 6 months, unstable angina, ventricular tachyarythmias requiring ongoing treatment, severe chronic obstructive pulmonary disease with hypoxemia, uncontrolled diabetes mellitus, or uncontrolled hypertension
  • Concomitant disease requiring prolonged use of corticosteroids > 1 month
  • Known hypersensitivity with anaphylactic reaction to humanized monoclonal antibodies or any of the study drugs According to the SmPC or investigator practice
  • Contraindication to use of Rituximab
  • Transformation to aggressive B-cell malignancy e.g. diffuse large cell lymphoma, Hodgkin lymphoma, or prolymphocytic leukaemia
  • Active bacterial, viral or fungal infection
  • Abnormal renal function with creatinine clearance < 60 ml/min calculated according to the Cockcroft and Gault formula
  • Total bilirubin, gamma glutamyltransferase or transaminase levels > 2.5 ULN.
  • Any coexisting medical or psychological condition that would preclude participation in the required study procedures
  • Patient with mental deficiency preventing proper understanding of the requirements of treatment.
  • Pregnant or breastfeeding women.
  • Adult under law-control
  • Fertile male and female patients who cannot or do not wish to use an effective method of contraception, during and for 12 months after the final treatment used for the purposes of the study.
  • No afiliate to social security

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Standard R-FC arm

Standard R-FC arm 6 cycles every 28 days

  • Cycle 1:

    • Rituximab : 375 mg/m² i.v on day 1
    • Fludarabine : 40 mg/m² per os, days 2-4, repeated every 28 days
    • Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days For patients with Leucocyte count > 25* G/L : rituximab in two equal doses at D1, D2

  • Cycle 2-6:

    • Rituximab: 500 mg/m² i.v on day 1, repeated every 28 days
    • Fludarabine : 40 mg/m² per os, days 2-4, repeated every 28 days
    • Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days
Drug: Rituximab
  • Cycle 1 Rituximab : 375 mg/m² i.v on day 1
  • Cycle 2-6 Rituximab:500 mg/m² i.v on day 1, repeated every 28 days
Other Names:
  • R
Drug: Rituximab
  • Prephase: Rituximab:500 mg on day 0, 2000 mg on days 1, 8, and D15
  • Cycle 1-6 cycle 1 beginning at D22: Rituximab: 500 mg/m2 i.v on day 1, repeated every 28 days
Other Names:
  • R
Drug: Cyclophosphamide
•FCR Cycle 1-6: Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days
Other Names:
  • C
Drug: Fludarabine
FCR Cycle 1-6: Fludarabine :40 mg/m² per os, days 2-4, repeated every 28 days
Other Names:
  • F
Experimental: DenseR-FC arm

DenseR-FC arm =1 prephase R Dense course +6 R-FC courses

  • Prephase:

    - Rituximab: 500 mg on day 0, 2000 mg on days 1, 8, and D15 For patients with Leucocyte count > 25* G/L : rituximab 250 mg D-1, D0 prephase

  • Cycle 1-6 (cycle 1 beginning at D22):

    • Rituximab: 500 mg/m2 i.v on day 1, repeated every 28 days
    • Fludarabine : 40 mg/m² per os, days 2-4, repeated every 28 days
    • Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days
Drug: Rituximab
  • Cycle 1 Rituximab : 375 mg/m² i.v on day 1
  • Cycle 2-6 Rituximab:500 mg/m² i.v on day 1, repeated every 28 days
Other Names:
  • R
Drug: Rituximab
  • Prephase: Rituximab:500 mg on day 0, 2000 mg on days 1, 8, and D15
  • Cycle 1-6 cycle 1 beginning at D22: Rituximab: 500 mg/m2 i.v on day 1, repeated every 28 days
Other Names:
  • R
Drug: Cyclophosphamide
•FCR Cycle 1-6: Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days
Other Names:
  • C
Drug: Fludarabine
FCR Cycle 1-6: Fludarabine :40 mg/m² per os, days 2-4, repeated every 28 days
Other Names:
  • F

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
complete response rates according to IWCLL 2008 guidelines with undetectable minimal residual disease
Time Frame: 9 months
CR MRD negative rate at 9 months = treatment evaluation surveillance of cumulative toxicities of high dose rituximab
9 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
To determine and compare the progression free survival PFS
Time Frame: 3 years
3 years
evaluate the immunophenotypic response rate after high dose Rituximab alone prephase in DenseR-FC
Time Frame: 9 months
Treatment evaluation
9 months
To evaluate FcyRs polymorphisms influence on clinical response
Time Frame: 9 months
R Dense arm treatment evaluation
9 months
To determine the pharmacokinetics of rituximab and determine the PK-PD relationship of rituximab based on biomarkers.
Time Frame: 12 months
12 months
To evaluate the safety profile of higher doses of rituximab
Time Frame: 41
5 months treatment and 36 months follow up
41
To determine the event-free survival EFS
Time Frame: 3 years
3 years
To determine and compare the disease-free survival DFS
Time Frame: 3 years
3 years
To determine the overall survival OS
Time Frame: 3 years
3 years
To determine the time to next treatment TTNT
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
French Innovative Leukemia Organisation

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Roche Pharma AG

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Guillaume CARTRON, MD PD, French Innovative Leukemia Organisation
  • Principal Investigator: Stephane LEPRETRE, MD, French Innovative Leukemia Organisation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 23, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 9, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 10, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 16, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 15, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CLL 2010 FMP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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